Skip to main content
SpringerLink
Log in

Characterization of a bifunctional β-lactamase/ribonuclease and its interaction with a chaperone-like protein in the pathogen Mycobacterium tuberculosis H37Rv

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Most mycobacteria appear to be naturally resistant to β-lactam antibiotics such as penicillin. However, very few β-lactamases and their regulation have been clearly characterized in Mycobacterium tuberculosis H37Rv. In this study, a unique bifunctional protein, Rv2752c, from M. tuberculosis showed both β-lactamase and RNase activities. Two residues, D184 and H397, appear to be involved in Zn2+-binding and are essential for the dual functions. Both activities are lost upon deletion of the C-terminal 100 a.a. long Rv2752c tail, which contains an additional loop when compared with the RNase J of Bacillus subtilis. A chaperone-like protein, Rv2373c, physically interacted with Rv2752c and inhibited both activities. This is the first report of characterization of a bifunctional β-lactamase and its regulation in mycobacteria. These data offered important clues for further investigation of the structure and function of microbial β-lactamases. Increased understanding of this protein will provide further insights into the mechanism of microbial drug resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

3-AT:

3-amino-1,2,4-triazole

GST:

glutathione-S-transferase

Ni-NTA:

Ni2+-nitrilotriacetate

References

  1. Fisher, J. F., Meroueh, S. O., and Mobashery, S. (2005) Chem. Rev., 105, 395–424.

    Article  PubMed  CAS  Google Scholar 

  2. Wilke, M. S., Lovering, A. L., and Strynadka, N. C. (2005) Curr. Opin. Microbiol., 8, 525–533.

    Article  PubMed  CAS  Google Scholar 

  3. Bush, K., Jacoby, G. A., and Medeiros, A. A. (1995) Antimicrob. Agents Chemother., 39, 1211–1233.

    PubMed  CAS  Google Scholar 

  4. Carfi, A., Pares, S., Duee, E., Galleni, M., Duez, C., Frere, J. M., and Dideberg, O. (1995) EMBO J., 14, 4914–4921.

    PubMed  CAS  Google Scholar 

  5. Orellano, E. G., Girardini, J. E., Cricco, J. A., Ceccarelli, E. A., and Vila, A. J. (1998) Biochemistry, 37, 10173–10180.

    Article  PubMed  CAS  Google Scholar 

  6. Fabiane, S. M., Sohi, M. K., Wan, T., Payne, D. J., Bateson, J. H., Mitchell, T., and Sutton, B. J. (1998) Biochemistry, 37, 12404–12411.

    Article  PubMed  CAS  Google Scholar 

  7. Garau, G., Bebrone, C., Anne, C., Galleni, M., Frere, J. M., and Dideberg, O. A. (2005) J. Mol. Biol., 345, 785–795.

    Article  PubMed  CAS  Google Scholar 

  8. Garrity, J. D., Carenbauer, A. L., Herron, L. R., and Crowder, M. W. (2004) J. Biol. Chem., 279, 920–927.

    Article  PubMed  CAS  Google Scholar 

  9. Wang, Z., and Benkovic, S. J. (1998) J. Biol. Chem., 273, 22402–22408.

    Article  PubMed  CAS  Google Scholar 

  10. De Seny, D., Heinz, U., Wommer, S., Kiefer, J. H., Meyer-Klaucke, W., Galleni, M., Frere, J., Bauer, R., and Adolph, H. W. (2001) J. Biol. Chem., 276, 45065–45078.

    Article  PubMed  Google Scholar 

  11. Rasia, R. M., and Vila, A. J. (2002) Biochemistry, 41, 1853–1860.

    Article  PubMed  CAS  Google Scholar 

  12. Bebrone, C., Delbruck, H., Kupper, M. B., Schlomer, P., Willmann, C., Frere, J. M., Fischer, R., Galleni, M., and Hoffmann, K. M. (2009) Antimicrob. Agents Chemother., 53, 4464–4471.

    Article  PubMed  CAS  Google Scholar 

  13. Fast, W., Wang, Z. G., and Benkovic, S. J. (2001) Biochemistry, 40, 1640–1650.

    Article  PubMed  CAS  Google Scholar 

  14. Hu, Z., Spadafora, L. J., Hajdin, C. E., Bennett, B., and Crowder, M. W. (2009) Biochemistry, 48, 2981–2999.

    Article  PubMed  CAS  Google Scholar 

  15. Even, S., Pellegrini, O., Zig, L., Labas, V., Vinh, J., and Putzer, H. (2005) Nucleic Acids Res., 33, 2141–2152.

    Article  PubMed  CAS  Google Scholar 

  16. Britton, R. A., Tingyi, W., Laura, S., Olivier, P., William, C. U., Nathalie, M., Crystal, T., Roula, D., and Ciaran, C. (2007) Mol. Microbiol., 63, 127–138.

    Article  PubMed  CAS  Google Scholar 

  17. Callebaut, I., Moshous, D., Mornon, J. P., and de Villartay, J. P. (2002) Nucleic Acids Res., 30, 3592–3601.

    Article  PubMed  CAS  Google Scholar 

  18. Nathalie, M., Lionel, B., Olivier, P., Roula, D., Tingyi, W., and Ciaran, C. (2007) Cell, 129, 681–692.

    Article  Google Scholar 

  19. Sierra-Gallay, I., Zig, L., Jamalli, A., and Putzer, H. (2008) Nat. Struct. Mol. Biol., 15, 206–212.

    Article  PubMed  Google Scholar 

  20. Feng, W., Cassidy, C., and James, C. S. (2006) Antimicrob. Agents Chemother., 50, 2762–2771.

    Article  Google Scholar 

  21. Nampoothiri, K. M., Rubex, R., Patel, A. K., Narayanan, S. S., Krishna, S., Das, S. M., and Pandey, A. (2008) J. Appl. Microbiol., 105, 59–67.

    Article  PubMed  CAS  Google Scholar 

  22. Tremblay, L. W., Hugonnet, J. E., and Blanchard, J. S. (2008) Biochemistry, 47, 5312–5316.

    Article  PubMed  CAS  Google Scholar 

  23. Cui, T., Zhang, L., Wang, X., and He, Z. G. (2009) BMC Genomics, 10, 118.

    Article  PubMed  CAS  Google Scholar 

  24. Gill, S. C., and von Hippel, P. H. (1989) Anal. Biochem., 182, 319–326.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang, L., Zhang, L., Liu, Y., Yang, S., Gao, C., Gong, H., Feng, Y., and He, Z. G. (2009) Proc. Natl. Acad. Sci. USA, 106, 7792–7797.

    Article  PubMed  CAS  Google Scholar 

  26. Zeng, J., Zhang, L., Li, Y., Wang, Y., Wang, M., Duan, X., and He, Z. G. (2010) Protein Expr. Purif., 69, 47–53.

    Article  PubMed  CAS  Google Scholar 

  27. Arnold, K., Bordoli, L., Kopp, J., and Schwede, T. (2006) Bioinformatics, 22, 195–201.

    Article  PubMed  CAS  Google Scholar 

  28. Kolev, N. G., Yario, T. A., Benson, E., and Steitz, J. A. (2008) EMBO Rep., 9, 1013–1018.

    Article  PubMed  CAS  Google Scholar 

  29. Massova, I., and Mobashery, S. (1998) Antimicrob. Agents Chemother., 42, 1–17.

    Article  PubMed  CAS  Google Scholar 

  30. Nampoothiri, K. M. (2003) J. Biotechnol., 2, 342–345.

    CAS  Google Scholar 

  31. Stewart, G. R., Robertson, B. D., and Young, D. B. (2004) Tuberculosis, 84, 180–187.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China

    Lei Sun, Lei Zhang, Hua Zhang & Zheng-Guo He

Authors
  1. Lei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zheng-Guo He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zheng-Guo He.

Additional information

Published in Russian in Biokhimiya, 2011, Vol. 76, No. 3, pp. 429–439.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, L., Zhang, L., Zhang, H. et al. Characterization of a bifunctional β-lactamase/ribonuclease and its interaction with a chaperone-like protein in the pathogen Mycobacterium tuberculosis H37Rv. Biochemistry Moscow 76, 350–358 (2011). https://doi.org/10.1134/S0006297911030096

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297911030096

Key words

Search

Navigation